FAM19A4/miR124-2 methylation in invasive cervical cancer: A retrospective cross-sectional worldwide study

Frederique J Vink, Chris J L M Meijer, Gary M Clifford, Mario Poljak, Anja Oštrbenk, Karl Ulrich Petry, Beate Rothe, Jesper Bonde, Helle Pedersen, Silvia de Sanjosé, Montserrat Torres, Marta Del Pino, Wim G V Quint, Kate Cuschieri, Elia Alcañiz Boada, Nienke E van Trommel, Birgit I Lissenberg-Witte, Arno N Floore, Albertus T Hesselink, Renske D M SteenbergenMaaike C G Bleeker, Daniëlle A M Heideman

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Abstract

Widespread adoption of primary human papillomavirus (HPV)-based screening has encouraged the search for a triage test which retains high sensitivity for the detection of cervical cancer and precancer, but increases specificity to avoid overtreatment. Methylation analysis of FAM19A4 and miR124-2 genes has shown promise for the triage of high-risk (hr) HPV-positive women. In this study, we assessed the consistency of FAM19A4/miR124-2 methylation analysis in the detection of cervical cancer in a series of 519 invasive cervical carcinomas (n = 314 cervical scrapes, n = 205 tissue specimens) from over 25 countries, using a quantitative methylation specific PCR (qMSP)-based assay (QIAsure Methylation Test®). Positivity rates stratified per histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region were calculated. In total, 510 of the 519 cervical carcinomas (98.3%; 95% CI: 96.7 - 99.2) tested FAM19A4/miR124-2 methylation-positive. Test positivity was consistent across the different subgroups based on cervical cancer histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region. In conclusion, FAM19A4/miR124-2 methylation analysis detects nearly all cervical carcinomas, including rare histotypes and hrHPV-negative carcinomas. These results indicate that a negative FAM19A4/miR124-2 methylation assay result is likely to rule out the presence of cervical cancer. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalInternational Journal of Cancer
DOIs
Publication statusE-pub ahead of print - 7 Aug 2019

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